Adjuvant immunotherapy for cancer: both dendritic cell-priming and check-point inhibitor blockade are required for immunotherapy.
Proc Jpn Acad Ser B Phys Biol Sci
; 94(3): 153-160, 2018.
Article
em En
| MEDLINE
| ID: mdl-29526974
ABSTRACT
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only â¼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis. For DC-priming, a therapeutic vaccine containing Toll-like receptor (TLR) agonists, namely a priming adjuvant, is a good candidate; however, a means for DC-targeting by TLR adjuvant therapy remains to be developed. TLR adjuvants usually harbor cytokine toxicity, which is a substantial barrier against drug approval. Here, we discuss the functional properties of current TLR adjuvants for cancer immunotherapy and introduce a TLR3-specific adjuvant (ARNAX) that barely induces cytokinemia in mouse models.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Adjuvantes Imunológicos
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Imunoterapia
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Jpn Acad Ser B Phys Biol Sci
Ano de publicação:
2018
Tipo de documento:
Article